DPP-4 Inhibitors as Treatments for Type 1 Diabetes Mellitus: A Systematic Review and Meta-Analysis

Objective. Several clinical studies have reported the application of dipeptidyl peptidase-4 (DPP-4) inhibitors as treatments for type 1 diabetes mellitus (T1DM). This study aims to review the outcomes of these existing studies and to discuss the therapeutic effects of DPP-4 inhibitors on T1DM. Methods. We thoroughly searched the Medline, Embase, PubMed, and Cochrane Library databases and ClinicalTrials.gov for studies concerning the use of DPP-4 inhibitors in patients with T1DM. Results. In preclinical trials, DPP-4 inhibitors improved the pathogenesis of T1DM. However, only a portion of the studies showed potential efficacy regarding clinical glycemic control and other clinical parameters. From this meta-analysis, pooled data from 5 randomized controlled trials revealed that the additional use of DPP-4 inhibitors resulted in a greater decrease in glycated hemoglobin A1c (HbA1c) levels (0.07%, 95% CI (−0.37%–0.23%)) than insulin monotherapy, although the decrease was not significant. A small decrease in postprandial glucose or insulin consumption was confirmed. Conclusion. Although DPP-4 inhibitors may be beneficial for T1DM, existing studies do not strongly support these positive effects in clinical practice. Further optimized clinical trials are needed

Methylprednisolone as Adjunct to Endovascular Thrombectomy for Large-Vessel Occlusion Stroke

Importance It is uncertain whether intravenous methylprednisolone improves outcomes for patients with acute ischemic stroke due to large-vessel occlusion (LVO) undergoing endovascular thrombectomy. Objective To assess the efficacy and adverse events of adjunctive intravenous low-dose methylprednisolone to endovascular thrombectomy for acute ischemic stroke secondary to LVO. Design, Setting, and Participants This investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 82 hospitals in China, enrolling 1680 patients with stroke and proximal intracranial LVO presenting within 24 hours of time last known to be well. Recruitment took place between February 9, 2022, and June 30, 2023, with a final follow-up on September 30, 2023.InterventionsEligible patients were randomly assigned to intravenous methylprednisolone (n = 839) at 2 mg/kg/d or placebo (n = 841) for 3 days adjunctive to endovascular thrombectomy. Main Outcomes and Measures The primary efficacy outcome was disability level at 90 days as measured by the overall distribution of the modified Rankin Scale scores (range, 0 [no symptoms] to 6 [death]). The primary safety outcomes included mortality at 90 days and the incidence of symptomatic intracranial hemorrhage within 48 hours. Results Among 1680 patients randomized (median age, 69 years; 727 female [43.3%]), 1673 (99.6%) completed the trial. The median 90-day modified Rankin Scale score was 3 (IQR, 1-5) in the methylprednisolone group vs 3 (IQR, 1-6) in the placebo group (adjusted generalized odds ratio for a lower level of disability, 1.10 [95% CI, 0.96-1.25]; P = .17). In the methylprednisolone group, there was a lower mortality rate (23.2% vs 28.5%; adjusted risk ratio, 0.84 [95% CI, 0.71-0.98]; P = .03) and a lower rate of symptomatic intracranial hemorrhage (8.6% vs 11.7%; adjusted risk ratio, 0.74 [95% CI, 0.55-0.99]; P = .04) compared with placebo. Conclusions and Relevance Among patients with acute ischemic stroke due to LVO undergoing endovascular thrombectomy, adjunctive methylprednisolone added to endovascular thrombectomy did not significantly improve the degree of overall disability.Trial RegistrationChiCTR.org.cn Identifier: ChiCTR210005172

Precision Landing Test and Simulation of the Agricultural UAV on Apron

Unmanned aerial vehicle (UAV) has been used to assist agricultural production. Precision landing control of UAV is critical for application of it in some specific areas such as greenhouses or livestock/poultry houses. For controlling UAV landing on a fixed or mobile apron/platform accurately, this study proposed an automatic method and tested it under three scenarios: (1) UAV landing at high operating altitude based on the GPS signal of the mobile apron; (2) UAV landing at low operating altitude based on the image recognition on the mobile apron; and (3) UAV landing progress control based on the fixed landing device and image detection to achieve a stable landing action. To verify the effectiveness of the proposed control method, apron at both stationary and mobile (e.g., 3 km/h moving speed) statuses were tested. Besides, a simulation was conducted for the UAV landing on a fixed apron by using a commercial poultry house as a model (135 L × 15 W × 3 H m). Results show that the average landing errors in high altitude and low altitude can be controlled within 6.78 cm and 13.29 cm, respectively. For the poultry house simulation, the landing errors were 6.22 ± 2.59 cm, 6.79 ± 3.26 cm, and 7.14 ± 2.41cm at the running speed of 2 km/h, 3 km/h, and 4 km/h, respectively. This study provides the basis for applying the UAV in agricultural facilities such as poultry or animal houses where requires a stricter landing control than open fields

Plasma Asprosin Concentrations Are Increased in Individuals with Glucose Dysregulation and Correlated with Insulin Resistance and First-Phase Insulin Secretion

Background. Adipokines are reported to participate in many common pathologic processes of glucose dysregulation, such as insulin resistance, β-cell dysfunction, and chronic inflammation. Objective. To detect the concentrations of plasma asprosin in subjects with impaired glucose regulation (IGR) and newly diagnosed type 2 diabetes (nT2DM) and its relationship to parameters of glucose and lipid metabolism, insulin resistance, and pancreatic β-cell function. Methods. 143 eligible participants were included and were divided into three groups including normal glucose regulation (NGR, n=52), IGR (n=40), and nT2DM group (n=51). The intravenous glucose tolerance test (IVGTT) and clinical and biochemical parameters were measured in all participants. Results. Plasma asprosin levels were higher in IGR (82.40 ± 91.06 ng/mL, P<0.001) and nT2DM (73.25 ± 91.69 ng/mL, P<0.001) groups compared with those in the NGR (16.22 ± 9.27 ng/mL) group, especially in IGR subjects. Correlation analysis showed that plasma asprosin levels were positively correlated with waist circumference (Wc), fasting plasma glucose (FPG), postchallenge plasma glucose (2hPG), HbA1c, triglyceride (TG), and homeostasis model assessment for insulin resistance (HOMA-IR) and negatively correlated with homeostasis model assessment for β-cell function (HOMA-β), area under the curve of the first-phase (0–10 min) insulin secretion (AUC), acute insulin response (AIR), and glucose disposition index (GDI) (all P<0.05). Multiple logistical regression analyses revealed that plasma asprosin concentrations were significantly correlated with IGR and nT2DM after controlling for age, sex, BMI, and WHR. Conclusions. Circulating asprosin might be a predictor of early diagnosis in DM and might be a potential therapeutic target for prediabetes and T2DM

Label-free in-vivo classification and tracking of red blood cells and platelets using Dynamic-YOLOv4 network

In-vivo flow cytometry is a noninvasive real-time diagnostic technique that facilitates continuous monitoring of cells without perturbing their natural biological environment, which renders it a valuable tool for both scientific research and clinical applications. However, the conventional approach for improving classification accuracy often involves labeling cells with fluorescence, which can lead to potential phototoxicity. This study proposes a label-free in-vivo flow cytometry technique, called dynamic YOLOv4 (D-YOLOv4), which improves classification accuracy by integrating absorption intensity fluctuation modulation (AIFM) into YOLOv4 to demodulate the temporal features of moving red blood cells (RBCs) and platelets. Using zebrafish as an experimental model, the D-YOLOv4 method achieved average precisions (APs) of 0.90 for RBCs and 0.64 for thrombocytes (similar to platelets in mammals), resulting in an overall AP of 0.77. These scores notably surpass those attained by alternative network models, thereby demonstrating that the combination of physical models with neural networks provides an innovative approach toward developing label-free in-vivo flow cytometry, which holds promise for diverse in-vivo cell classification applications

DPP-4 Inhibitors as Treatments for Type 1 Diabetes Mellitus: A Systematic Review and Meta-Analysis

Objective. Several clinical studies have reported the application of dipeptidyl peptidase-4 (DPP-4) inhibitors as treatments for type 1 diabetes mellitus (T1DM). This study aims to review the outcomes of these existing studies and to discuss the therapeutic effects of DPP-4 inhibitors on T1DM. Methods. We thoroughly searched the Medline, Embase, PubMed, and Cochrane Library databases and ClinicalTrials.gov for studies concerning the use of DPP-4 inhibitors in patients with T1DM. Results. In preclinical trials, DPP-4 inhibitors improved the pathogenesis of T1DM. However, only a portion of the studies showed potential efficacy regarding clinical glycemic control and other clinical parameters. From this meta-analysis, pooled data from 5 randomized controlled trials revealed that the additional use of DPP-4 inhibitors resulted in a greater decrease in glycated hemoglobin A1c (HbA1c) levels (0.07%, 95% CI (−0.37%–0.23%)) than insulin monotherapy, although the decrease was not significant. A small decrease in postprandial glucose or insulin consumption was confirmed. Conclusion. Although DPP-4 inhibitors may be beneficial for T1DM, existing studies do not strongly support these positive effects in clinical practice. Further optimized clinical trials are needed

CD9 Counteracts Liver Steatosis and Mediates GCGR Agonist Hepatic Effects

Abstract Glucagon receptor (GCGR) agonism offers potentially greater effects on the mitigation of hepatic steatosis. However, its underlying mechanism is not fully understood. Here, it screened tetraspanin CD9 might medicate hepatic effects of GCGR agonist. CD9 is decreased in the fatty livers of patients and upregulated upon GCGR activation. Deficiency of CD9 in the liver exacerbated diet‐induced hepatic steatosis via complement factor D (CFD) regulated fatty acid metabolism. Specifically, CD9 modulated hepatic fatty acid synthesis and oxidation genes through regulating CFD expression via the ubiquitination‐proteasomal degradation of FLI1. In addition, CD9 influenced body weight by modulating lipogenesis and thermogenesis of adipose tissue through CFD. Moreover, CD9 reinforcement in the liver alleviated hepatic steatosis, and blockage of CD9 abolished the remission of hepatic steatosis induced by cotadutide treatment. Thus, CD9 medicates the hepatic beneficial effects of GCGR signaling, and may server as a promising therapeutic target for hepatic steatosis

Spintronic terahertz metasurface emission characterized by scanning near-field nanoscopy

Understanding the ultrafast excitation, detection, transportation, and manipulation of nanoscale spin dynamics in the terahertz (THz) frequency range is critical to developing spintronic THz optoelectronic nanodevices. However, the diffraction limitation of the sub-millimeter waves – THz wavelengths – has impaired experimental investigation of spintronic THz nano-emission. Here, we present an approach to studying laser THz emission nanoscopy from W|CoFeB|Pt metasurfaces with ∼60-nm lateral spatial resolution. When comparing with statistic near-field THz time-domain spectroscopy with and without the heterostructures on fused silica substrates, we find that polarization- and phase-sensitive THz emission nanoscopy is more sensitive than the statistic THz scattering intensity nanoscopy. Our approach opens explorations of nanoscale ultrafast THz spintronic dynamics in optically excited metasurfaces

Total Structure Determination of Au₂₁(S-Adm)₁₅ and Geometrical/Electronic Structure Evolution of Thiolated Gold Nanoclusters

The larger size gold nanoparticles typically adopt a face-centered cubic (fcc) atomic packing, while in the ultrasmall nanoclusters the packing styles of Au atoms are diverse, including fcc, hexagonal close packing (hcp), and body-centered cubic (bcc), depending on the ligand protection. The possible conversion between these packing structures is largely unknown. Herein, we report the growth of a new Au₂₁(S-Adm)₁₅ nanocluster (S-Adm = adamantanethiolate) from Au₁₈(SR)₁₄ (SR = cyclohexylthiol), with the total structure determined by X-ray crystallography. It is discovered that the hcp Au₉-core in Au₁₈(SR)₁₄ is transformed to a fcc Au₁₀-core in Au₂₁(S-Adm)₁₅. Combining with density functional theory (DFT) calculations, we provide critical information about the growth mechanism (geometrical and electronic structure) and the origin of fcc-structure formation for the thiolate-protected gold nanoclusters